This application outlines the establishment of the Rochester, New York and an International Unit in Rio de Janeiro, Brazil. The two Units are highly complementary and blend the expertise and experience of two very successful ongoing programs: the AVEU at the University of Rochester (UR) and the HIVNET site at the Universidade Federal do Rio de Janeiro (UFRJ). The UR AVEU has over ten years of experience in the performance of preventive HIV vaccine trials, with an emphasis on Phase I/II investigations, whereas the UFRJ HIVNET has developed expertise in the establishment of cohorts at high-risk of HIV infection, and in the conduct of large scale clinical trials. Investigators at both the Domestic and International Units cave made major scientific and administrative contributions directly relevant to the progress of HIV vaccine research, .and plan to continue this tradition in the HVTN. The proposed HVTU will contribute actively to the HVTN Scientific agenda, and will conduct Phase I, II, and III investigations of candidate HIV vaccines in both domestic and international settings. The Rochester-Rio HVTU investigators plan to propose, chair, and participate in protocols that evaluate (l) novel immunogens designed to stimulate neutralizing antibodies against primary isolates, (2) vaccine candidates designed to induce high levels of CTL activity and other cellular responses, (3) approaches to improvement if mucosal immunity, (4) replicating viral and bacterial vectors, (5) different routes of vaccine administration, (6) new inmunologic assays, and (7) the impact of host factors and viral variation on vaccine efficacy. In the first year of the project period, the Rochester-Rio HVTU plans to participate in 6 Phase I and 2 Phase II HIV vaccine trials, and to enroll 150 subjects, including 90 at low risk for HIV infection and 60 at high risk. Rochester- Rio investigators also -tend to participate actively in Phase III studies as they become available, and have presented an expansion plan that will draw on a total population base of nearly 19 million people and enable the HVTU to easily enroll 1,000 subjects annually in efficacy trials.